18-331713-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_130386.3(COLEC12):c.2018G>A(p.Arg673His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000582 in 1,613,822 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000047 (1 hom.)
• Consequence: COLEC12 NM_130386.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.400

Genes affected

COLEC12 (HGNC:16016): (collectin subfamily member 12) This gene encodes a member of the C-lectin family, proteins that possess collagen-like sequences and carbohydrate recognition domains. This protein is a scavenger receptor that displays several functions associated with host defense. It can bind to carbohydrate antigens on microorganisms, facilitating their recognition and removal. It also mediates the recognition, internalization, and degradation of oxidatively modified low density lipoprotein by vascular endothelial cells. [provided by RefSeq, May 2018]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.032876402).
• BP6: Variant 18-331713-C-T is Benign according to our data. Variant chr18-331713-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2594755.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COLEC12	NM_130386.3	c.2018G>A	p.Arg673His	missense_variant	8/10	ENST00000400256.5
COLEC12	XM_011525741.3	c.1967G>A	p.Arg656His	missense_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COLEC12	ENST00000400256.5	c.2018G>A	p.Arg673His	missense_variant	8/10	1	NM_130386.3	P1
COLEC12	ENST00000582147.1	n.3824G>A		non_coding_transcript_exon_variant	7/9	5

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.0000636 AC: 16 AN: 251488 Hom.: 1 AF XY: 0.0000809 AC XY: 11 AN XY: 135918

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.0000465 AC: 68 AN: 1461656 Hom.: 1 Cov.: 29 AF XY: 0.0000536 AC XY: 39 AN XY: 727142

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.000268

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000290

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000162

Gnomad4 OTH exome AF: 0.000132

GnomAD4 genome AF: 0.000171 AC: 26 AN: 152166 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74334

Gnomad4 AFR AF: 0.0000483

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000192

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.000478

Alfa AF: 0.000115 Hom.: 0

Bravo AF: 0.000321

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000247 AC: 3

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 17, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.79
Cadd	Benign	7.0
Dann	Benign	0.62
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0098	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.47	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.016
Sift	Benign	0.45	T
Sift4G	Benign	0.16	T
Polyphen		0.015	B
Vest4		0.087
MVP		0.13
MPC		0.29
ClinPred		0.012	T
GERP RS		-0.59
Varity_R		0.069
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs373227938; hg19: chr18-331713; COSMIC: COSV68373152;